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E Purucker

Publications and source records attributed to E Purucker.

14 recordsLinked to original sources
PubMed2003

Effect of glutathione depletion and hydrophilic bile acids on hepatic acute phase reaction in rats with extrahepatic cholestasis.

BACKGROUND: Extrahepatic cholestasis by biliary obstruction induces an acute phase reaction in the liver. It is a complex process involving cytokines, hormones and growth factors. To determine whether the regulation of acute phase proteins (APP) in cholestasis depends on glutathione (GSH), the effect of buthionine sulfoximine-induced (BSO-induced) GSH depletion on the expression of various APP was studied. In addition, we determined the influence of hepatoprotective bile acids on hepatic APP and underlying cytokine events. METHODS: Liver samples of bile-duct-ligated or sham-operated rats were examined. mRNA expression was quantified by densitometric analysis of Northern blots. RESULTS: Expression of APP increased 2-5-fold in bile-duct-ligated rats as compared to sham-operated controls. This acute phase reaction remained similar independently of whether cholestasis occurred for 5 days or 3 weeks. In contrast to alpha2-macroglobulin and tissue inhibitor of metalloproteinases-1 (TIMP-1), mRNA levels of both beta-fibrinogen and haptoglobin were significantly up-regulated after GSH depletion by BSO in cholestasis. Feeding of ursodeoxycholic and iso-ursodeoxycholic acid markedly down-regulated alpha2-macroglobulin and TIMP-1 expression in cholestasis but did not affect overexpression of beta-fibrinogen and haptoglobin. Cholestasis leads to an increased APP expression accompanied by an increased expression of inflammatory cytokines (IL-6, TNF-alpha). After feeding of hydrophilic bile acids, increases in inflammatory cytokines were abrogated. CONCLUSIONS: We show that GSH is involved in the acute phase reaction during obstructive cholestasis. In addition, bile acids might selectively ameliorate the acute phase response by reducing expression of the APP not affected by GSH depletion (alpha2-macroglobulin and TIMP-1).

Acute-Phase Proteins↗
PubMed2001

Metabolism and effects on cholestasis of isoursodeoxycholic and ursodeoxycholic acids in bile duct ligated rats.

Isoursodeoxycholic acid (isoUDCA), the 3 beta-epimer of ursodeoxycholic acid (UDCA), may have pharmaceutical potential because of its similar hydrophilicity and in vitro cytoprotection as compared with UDCA. We compared metabolism and effects on cholestasis of UDCA and isoUDCA in experimental cholestasis in rats. Cholestasis was induced by bile duct ligation. For bile flow and biliary bile acid analysis, UDCA or isoUDCA were infused intraduodenally. For the study of chronic effects, chow was supplemented with 2.5 g/kg UDCA or isoUDCA for 3 weeks. Sham-operated animals served as controls. IsoUDCA became completely converted to UDCA in the liver. Choleresis and biliary bile acids were the same after the intraduodenal administration of either compound. Oral administration of UDCA or isoUDCA significantly improved liver biochemistry but not clinical and histological parameters in chronic cholestasis. The decrease of serum cholic acid in control animals was more pronounced after isoUDCA (-93%) than after UDCA (-76%). Only after UDCA, this decrease was compensated by increases of UDCA, beta-muricholic acid (MCA), and Delta(22)-beta-MCA. Our results show that isoUDCA has the same effect on choleresis and liver biochemistry as UDCA. IsoUDCA features pro-drug characteristics of UDCA and causes compared to the latter lower serum bile acid concentrations in non-cholestatic animals.

Animals↗
PubMed1998

Glutathione status in liver and plasma during development of biliary cirrhosis after bile duct ligation.

We do not know much about the changes that occur in reduced (GSH) and oxidized (GSSG) glutathione in the development of liver cirrhosis. Therefore, we investigated the glutathione redox system during development of liver cirrhosis after bile-duct ligation in rats. We compared the GSH and GSSG content of liver and plasma between bile-duct-ligated rats and sham-operated controls 6 and 24 h and 5, 15, 23, and 38 days after operation. Compared to controls (x +/- SD: 6.07 +/- 0.52 mumol/g wet wt.), liver GSH significantly increased 24 h (+ 37%) and 5 days (+ 53%) after bile-duct ligation. Thereafter, GSH continuously declined to 4.25 +/- 0.64 mumol/g (-31%; P < 0.001) at the end of the observation period after 38 days. The GSH turnover in 5-day bile-duct-ligated rats with high GSH concentrations was not significantly different than in sham-operated controls (16 nmol/min per g after bile-duct ligation and 15 nmol/min per g in controls). GSSG (211 +/- 42 nmol/g wet wt. in controls) was significantly lower 6 and 24 h after bile-duct ligation (-34% and -43%, respectively). Thereafter, GSSG increased and was about 100% higher than in controls after 23 and 38 days. The relation of GSSG to GSH in liver continuously increased from 3.4 to 20.5% after bile-duct ligation. The course of plasma GSH (9.57 +/- 0.79 mumol/l) paralleled hepatic GSH on a lower level: + 14% at day 5, -41% at day 15 and -51% at the end of the observation period. Plasma GSSG (0.99 +/- 0.31 mumol/l) was inversely related to liver GSSG: there were increased concentrations early after bile duct ligation (day 5: + 91%) and reduced concentrations (-44%) at the end of the observation period. Dynamic changes of the glutathione status occur in the development of liver cirrhosis after bile-duct ligation. These changes are consistent with increased oxidative stress in the liver and a deficit of transporting GSSG from the cells into plasma.

Animals↗
PubMed1997

Study of human isoursodeoxycholic acid metabolism.

BACKGROUND/AIMS: The aim of this study was to examine the metabolism of isoursodeoxycholic acid (isoUDCA) in humans. METHODS: IsoUDCA was synthesized of >99% purity and administered orally for 1 week, 3 x 250 mg/day, to six healthy male subjects. Bile acids were extracted from duodenal bile, serum, and 24-h urine samples collected before and at the end of the study period, separated into groups of conjugates, and analyzed by gas chromatography-mass spectrometry and fast atom bombardment mass spectrometry. RESULTS: IsoUDCA was tolerated without any side effect. Liver function tests did not change. Bile acid concentrations (mean+/-SEM) increased from 11.9+/-1.87 to 15.3+/-1.37 mmol/l in bile (n.s.), and from 3.4+/-0.10 to 6.8+/-0.43 micromol/l in serum (p<0.05). Urinary excretion of bile acids increased from 5.3+/-0.29 to 82.2+/-7.84 micromol/24 h (p<0.01). All changes were due to significant increases of isoUDCA and UDCA in bile, serum and urine, and of 3-dehydro-UDCA, the 3-oxo intermediate of isomerization, in bile and in serum. The relative enrichments of isoUDCA, UDCA, and 3-dehydro-UDCA, were: in bile, 2.2%, 25.7%, and 0.7%; in serum, 24.7%, 23.5%, and 6.1%; and in urine, 83.7%, 2.0%, and 2.4%. Whereas 78% of serum isoUDCA was unconjugated, 93-94% of biliary and urinary isoUDCA was conjugated with N-acetylglucosamine. CONCLUSIONS: This study indicates good tolerance and significant intestinal absorption of orally administered isoUDCA. IsoUDCA is extensively isomerized, probably both by intestinal and hepatic enzymes to yield UDCA which became the major biliary compound. In vitro, using the human hepatoblastoma cell line Hep G2, isoUDCA was found to be cytoprotective towards ethanol-induced cell injuries.

Adult↗
PubMed1997

TIMP expression in toxic and cholestatic liver injury in rat.

BACKGROUND/AIMS: Hepatic fibrosis is a dynamic pathological process with a net accumulation of extracellular matrix proteins. Recent evidence suggests that besides their increased synthesis, inhibition of matrix degradation plays a significant role. ECM degradation occurs via metalloproteinases which are inhibited in situ by specific tissue inhibitors of metalloproteinases (TIMPs). The aim of our studies was to determine the expression of TIMPs during toxic liver injury and cholestatic liver injury leading to fibrosis. METHODS: We examined the expression of TIMP-1, -2 and -3 in two different rat models for liver injury (intraperitoneal CCl4 injection and bile duct ligation) by Northern blot analysis and in situ hybridization. For comparison, the mRNA expression of the acute phase protein haptoglobin was measured. RESULTS: TIMP-1 was increased during the early phase of toxic liver injury and in cholestasis. Its expression occurred predominantly in areas of inflammation, in hepatocytes, and in mesenchymal and endothelial cells. There was a slight upregulation of TIMP-2 expression during cholestasis. TIMP-3 was not detected at all. CONCLUSIONS: Our results emphasize an involvement of TIMP-1 in matrix homeostasis, indicating its possible participation in liver fibrosis.

Animals↗
PubMed1995

Glutathione in plasma, liver, and kidney in the development of CCl4-induced cirrhosis of the rat.

Plasma glutathione is markedly decreased in human cirrhosis of the liver. This decrease is said to be caused by reduced concentrations of liver glutathione. However, several studies on hepatic glutathione have revealed its concentrations to be unchanged, decreased, or even elevated. To test these inconsistencies we investigated the glutathione status of plasma, liver, and kidney in rats chronically exposed to carbon tetrachloride (CCl4). After 14 weeks of CCl4 treatment, histological examination revealed progressive cirrhotic transformation. After 20 weeks, complete micro-nodular cirrhosis was present and distinct ascites had developed. Plasma reduced glutathione (GSH) decreased by 34% in the early and by 44% in the late group, paralleled by a 65% and 76% decrease of plasma oxidized glutathione (GSSG). Liver GSH in early stages of cirrhosis was reduced by 49%, but in late cirrhosis it did not differ from controls. In contrast, liver GSSG increased by 35% in the early and by 191% in the late group. Kidney GSH increased by 14% in early and 44% in late stage cirrhosis. Kidney GSSG was unchanged in the early group, but increased by 18% in the late group. The decrease of plasma GSH and GSSG is closely related to the severity of experimental cirrhosis and inversely related to an increase of hepatic oxidized glutathione. The hepatic content of reduced glutathione, however, is decreased in early cirrhosis only. According to these results the inconsistent findings in man could be due to differences in the stages of cirrhosis in the patients. The increase in kidney glutathione is a new finding that needs further investigation, but it may probably be related to kidney dysfunction in liver disease.

Animals↗
PubMed1992

Effect of hyperbaric oxygen treatment and perfluorochemical administration on glutathione status of the lung.

Exposure to hyperoxia, especially under hyperbaric conditions, causes an enhanced oxidative stress particularly in lung tissue. To test the potential hazardous effect of either a single or repeated hyperbaric oxygen treatment (HBO) on the cellular defence system the glutathione status of lung tissue from rats exposed to HBO was investigated. When daily exposed to 2.5 ATA of > 95% O2 for 90 min over 8 or 14 days the content of reduced glutathione in lung tissue (GSH) increased by 16-19%. Oxidized glutathione (GSSG) tended to increase after 8 days and was 56% higher after 14 days. While the GSSG/GSH ratio was unchanged after 8 days, it increased by 39% after 14 days. Thus, the GSH increase after 8 days can be understood as a adaptive process to protect the lung from oxidative stress. The distinct increment of the cellular GSSG that lead to an increase of the GSSG/GSH ratio after 14 days reflects a situation, in which the cellular defence system is overwhelmed by oxidative stress. The additional pretreatment with perfluorochemicals in a dose of 2g/kg every second day aggravated the observed changes (GSH +39-19%, GSSG +118%). In a second experiment rats were exposed to a single session with 7 ATA of O2 for 60 min. GSH in the lungs increased for 40%, it was not elevated by PFC. However, GSSG increased to a much higher degree in untreated as well as in PFC-treated animals (+240%, +163%), elevating the ratio GSSG/GSH markedly (+145%, +176%). Allopurinol given as radical scavenger in a dose of 50 mg/kg was able to suppress the increased oxidative stress widely. Thus adaptive and overloading processes are involved under the treatment with increased oxygen pressures. As the administration of PFC aggravates the observed changes, a still increased blood oxygen offer must be considered as the causative agent. A radical scavenger is capable to suppress the increased oxidative stress widely.

Animals↗
PubMed1992

Combination of treatment with perfluorochemicals and free radical scavengers.

P-cyclohexylmorpholine, given as oxygen carrier of second generation, was tested in two experimental models: the ischemic intestine and the lung under hyperbaric oxygen condition. In both instances in separated groups either alpha-tocopherol or allopurinol was additionally given as oxygen free radical scavenger. The thiobarbituric acid reaction (TBAR) was used as screening test for the occurrence of lipid peroxidation in organ probes; further the content of glutathione in reduced (GSH) and oxidized form (GSSG) was determined. Whereas only slight increases of TBAR substances and GSSG could be found compared to controls, the effect of the administrated scavenging drugs was very impressive: they could suppress nearly totally the effect of an enhanced oxidative stress.

Animals↗
PubMed1991

Differences in glutathione status and lipid peroxidation of red and white muscles: alterations following ischemia and reperfusion.

Glutathione status and products from lipid peroxidation [measured as thiobarbituric acid reactive substances (TBARS)] were determined in red and white muscle tissue of the rat. Marked differences between both muscle types were found in reduced glutathione (GSH) and oxidized glutathione (GSSG) content, exhibiting 163% and 183%, respectively, higher levels in red than in white muscle tissue, while the ratio of GSSG/GSH showed no differences. These characteristics may be due to an adaptive mechanism related to the 48% higher baseline level of TBARS in red muscle tissue. Immediately after 4 h of tourniquet-ischemia GSH, GSSG, and TBARS were increased (16%, 32%, 45% in white muscle; 19%, 49%, and 42% in red muscle, respectively), whereas the GSSG/GSH ratio remained unchanged. During the subsequent reperfusion period, GSH decreased within 2 h by 39% in white and 89% in red muscle to a minimal level of 5 mmol/g protein in both types of muscle. No recovery from the depletion was observed up to 12 h of reperfusion. The GSH decrease was parallelled by a marked increase of the GSSG/GSH ratio (150% in white and 450% in red muscle) and followed by about 150% increase in TBARS in both muscle types. This suggests that the increase in damaging TBARS is a secondary event after depletion of cellular antioxidants. Treatment of the animals during the reperfusion period with methyl-prednisolone, deferoxamine, or superoxide dismutase and catalase did not prevent the GSH decrease, but were effective in reducing the GSSG/GSH ratio to near normal and reducing the TBARS increase by about 50%.

Animals↗
PubMed1990

Hepatic efflux and renal extraction of plasma glutathione: marked differences between healthy subjects and the rat.

Hepatic efflux of glutathione accounts for almost 85% of the plasma level in the rat. However, the expected high concentration in the hepatic vein in man has not been demonstrated as yet. Our findings in ten patients without liver dysfunction reveal that substantial translocation of glutathione from the liver to the plasma does not occur. The removal rate of circulating glutathione by the kidney is far lower in man than in the rat (49.5% vs 84.6%). Moreover, the inferior vena cava in man contains more circulating glutathione than the artery, which is not consistent with the results obtained in the rat. Furthermore, the plasma concentration in man is about one tenth of that in the animals. These results clearly indicate that species-specific differences in the overall biosynthesis and metabolism of the tripeptide occur, resulting in marked variations in its plasma concentration.

Adult↗
PubMedDate not supplied

Hepatic portal venous gas following emergency endoscopic sclerotherapy of gastric varices.

Hepatic portal venous gas (HPVG) is a rare condition, usually associated with extended bowel necrosis or intra-abdominal infection. Herein, we report a case of HPVG following endoscopic sclerotherapy for bleeding gastric varices. A 50-year-old female with a history of alcoholic liver disease was referred to our hospital because of hematemesis. Emergency endoscopic sclerotherapy was performed to control bleeding gastric varices. Twelve hours later, HPVG was demonstrated by ultrasound and confirmed by duplex sonography, which spontaneously resolved 2 hours later. The patient remained well throughout this time, and was released with no major sequelae. This case supports the view that HPVG can also present as a benign finding, in particular, following diagnostic and therapeutic procedures of the gut. The underlying cause determines the clinical significance and prognosis of HPVG.

Acute Disease↗